The objectives of this research are: 1) to elucidate the structure of human fibrinogen. 2) to provide information relating to physiologic and pathologic pathways of fibrinogen metabolism. 3) to relate clinical and functional abnormalities of familial fibrinogen disorders to their primary structure. 4) to study the nature and function of non-fibrinogen plasma proteins such as "cold insoluble globulin" (CI-globulin) which interact with fibrinogen. To accomplish these objectives the nature of the primary structure of fibrinogen will be probed by analyses of intermediate and advanced plasmic "core" derivatives and non-core fragments. Comparison of "core" derivatives with circulating fibrinogen catabolites will be made to elucidate the pathways of catabolism and to examine the possibility that certain of these pathways may be mediated by plasmin or plasmin-like enzymes. Analyses of normally ocurring fibrinogen variant chains will be pursued to reveal the nature of the charge differences discovered between such chains. Similarly, analyses of familial fibrinogen abnormalities (e.g., Paris I) will be carried out to identify the molecular basAs for the dysfunction. Characterization of human CI-globulin will be carried out to shed light on the nature of its function. An attempt will be made to establish an animal model for the study of CI-globulin turnover and function in rabbits.